Publications by authors named "Hyo Jung Kim"

466 Publications

Development of a new risk stratification system for patients with newly diagnosed multiple myeloma using R-ISS and F-FDG PET/CT.

Blood Cancer J 2021 Dec 1;11(12):190. Epub 2021 Dec 1.

Department of Hematology-Oncology, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, South Korea.

In multiple myeloma (MM), a high number of focal lesions (FL) detected using positron emission tomography/computed tomography (PET/CT) was found to be associated with adverse prognosis. To design a new risk stratification system that combines the Revised International Staging System (R-ISS) with FL, we analyzed the data of 380 patients with newly diagnosed MM (NDMM) who underwent F-fluorodeoxyglucose (F-FDG) PET/CT upon diagnosis. The K-adaptive partitioning algorithm was adopted to define subgroups with homogeneous survival. The combined R-ISS with PET/CT classified NDMM patients into four groups: R-ISS/PET stage I (n = 31; R-ISS I with FL ≤ 3), stage II (n = 156; R-ISS I with FL > 3 and R-ISS II with FL ≤ 3), stage III (n = 162; R-ISS II with FL > 3 and R-ISS III with FL ≤ 3), and stage IV (n = 31; R-ISS III with FL > 3). The 2-year overall survival rates for stages I, II, III, and IV were 96.7%, 89.8%, 74.7%, and 50.3%. The 2-year progression-free survival rates were 84.1%, 64.7%, 40.8%, and 17.1%, respectively. The new R-ISS/PET was successfully validated in an external cohort. This new system had a remarkable prognostic power for estimating the survival outcomes of patients with NDMM. This system helps discriminate patients with a good prognosis from those with a poor prognosis more precisely.
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http://dx.doi.org/10.1038/s41408-021-00577-2DOI Listing
December 2021

Real-World Data from a Refractory Triple-Negative Breast Cancer Cohort Selected Using a Clinical Data Warehouse Approach.

Cancers (Basel) 2021 Nov 21;13(22). Epub 2021 Nov 21.

Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.

Purpose: Triple-negative breast cancer (TNBC) is well known for its aggressive course and poor prognosis. In this study, we sought to investigate clinical, demographic, and pathologic characteristics and treatment outcomes of patients with refractory, metastatic TNBC selected by a clinical data warehouse (CDW) approach.

Patients And Methods: Data were extracted from the real-time breast cancer registry integrated into the Data Analytics and Research Window for Integrated Knowledge C (DARWIN-C), the CDW of Samsung Medical Center. Between January 1997 and December 2019, a TNBC cohort was searched for in the breast cancer registry, which includes records from more than 40,000 patients. Among them, cases of pathologically confirmed metastatic TNBC (mTNBC) were selected as the cohort group ( = 451). The extracted data from the registry via the CDW platform included clinical, pathological, laboratory, and chemotherapy information. Refractory TNBC was defined as confirmed distant metastasis within one year after adjuvant treatment.

Results: This study comprised a total of 451 patients with mTNBC, including 69 patients with de novo mTNBC, 131 patients in the nonrefractory TNBC group with confirmed stage IV disease after one year of adjuvant treatment, and 251 patients with refractory mTNBC, whose disease recurred as stage IV within one year after completing adjuvant treatment. The refractory mTNBC cohort was composed of patients with disease that recurred at stage IV after surgery (refractory mTNBC after surgery) ( = 207) and patients in whom metastasis was confirmed during neoadjuvant chemotherapy (unresectable TNBC due to progression during neoadjuvant chemotherapy) ( = 44). Patients in the refractory mTNBC group were younger than those in the nonrefractory group (median age 46 vs. 51 years; < 0.001). Considering the pathological findings, the refractory group had a greater proportion of cases with Ki-67 ≥ 3+ than did the nonrefractory group (71% vs. 47%; = 0.004). During a median 8.4 years of follow-up, the overall survival was 24.8 months in the nonrefractory mTNBC group and 14.3 months in the refractory mTNBC group ( < 0.001), and the median progression-free survival periods were 6.2 months and 4.2 months, respectively ( < 0.001). The median disease-free survival period was 30.1 months in the nonrefractory mTNBC group and only 7.6 months in the refractory mTNBC group. Factors related to metastatic sites affecting overall survival were liver metastasis at diagnosis ( < 0.001) and leptomeningeal involvement ( = 0.001).

Conclusions: We revealed that patients with refractory mTNBC had a much poorer prognosis among all mTNBC cases and described the characteristics of this patient group.
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http://dx.doi.org/10.3390/cancers13225835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8616548PMC
November 2021

Resolving Atomic-Scale Interactions in Non-Fullerene Acceptor Organic Solar Cells with Solid-State NMR Spectroscopy, Crystallographic Modelling, and Molecular Dynamics Simulations.

Adv Mater 2021 Nov 24:e2105943. Epub 2021 Nov 24.

University of Lille, CNRS, Centrale Lille Institut, Univ. Artois, UMR 8181, Unité de Catalyse et Chimie du Solide, Lille, F-59000, France.

Fused-ring core non-fullerene acceptors (NFAs), designated "Y-series", have enabled high-performance organic solar cells (OSCs) achieving over 18% power conversion efficiency (PCE). Since the introduction of these NFAs, much effort has been expended to understand the reasons for their exceptional performance. While several studies have identified key optoelectronic properties that govern high PCEs, little is known about the molecular level origins of large variations in performance, spanning from 5 to 18% PCE, e.g., in the case of PM6:Y6 OSCs. Here, we introduce a combined solid-state NMR, crystallography, and molecular modelling approach to elucidate the atomic-scale interactions in Y6 crystals, thin films, and PM6:Y6 bulk heterojunction (BHJ) blends. We show the Y6 morphologies in BHJ blends are not governed by the morphology in neat films or single crystals. Notably, PM6:Y6 blends processed from different solvents self-assemble into different structures and morphologies, whereby the relative orientations of the sidechains and end groups of the Y6 molecules to their fused-ring cores play a crucial role in determining the resulting morphology and overall performance of the solar cells. The molecular-level understanding of BHJs enabled by this approach will guide the engineering of next-generation NFAs for stable and efficient OSCs. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/adma.202105943DOI Listing
November 2021

Efficacy of nilotinib in monozygotic twins with spinocerebellar ataxia type 6.

J Neurol 2021 Nov 17. Epub 2021 Nov 17.

Department of Neurology, College of Medicine, Dizziness Center, Seoul National University Bundang Hospital, Seoul National University, 173-82 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 13620, South Korea.

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http://dx.doi.org/10.1007/s00415-021-10895-xDOI Listing
November 2021

Vestibular impairments in episodic ataxia type 2.

J Neurol 2021 Oct 28. Epub 2021 Oct 28.

Department of Neurology, Pusan National University Hospital, Pusan National University School of Medicine and Biomedical Research Institute, Busan, South Korea.

Episodic ataxia type 2 (EA2) can present diverse ocular motor abnormalities, but few studies have systematically evaluated vestibular function during the interictal periods. This study aimed to determine vestibular impairments in patients with EA2 during the interictal periods. We recruited 17 patients with genetically confirmed EA2 (10 men, age range  =  16-85 years, median  =  32 years). We systematically evaluated the vestibular function by measuring the semicircular canals (SCCs) function with bithermal caloric tests, rotatory chair test, and video head impulse test (vHIT), and the otolith function with subjective visual vertical (SVV) tilt and variability, and cervical and ocular vestibular-evoked myogenic potentials (VEMPs). Patients with EA2 commonly showed abnormal VOR responses at least for one SCC with high-acceleration, high-frequency head impulses (14/16, 88%), and impaired visual-vestibular interaction (7/12, 58%). In response to low acceleration and frequency stimuli, the VOR gains were generally normal. The majority of EA2 patients had impairments in at least one of the otolith function tests (13/16, 81%): SVV tilt or variability (7/14, 50%), oVEMP (8/15, 53%), and cVEMP (4/16, 25%). Vestibular impairments are common in EA2 even during the interictal periods. Selective decrease in the VOR responses during higher acceleration stimuli along with impaired visual-vestibular interaction and otolith function suggests degeneration of the vestibulocerebellum or vestibular nuclei.
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http://dx.doi.org/10.1007/s00415-021-10856-4DOI Listing
October 2021

Intraoperative radiation therapy induces immune response activity after pancreatic surgery.

BMC Cancer 2021 Oct 12;21(1):1097. Epub 2021 Oct 12.

Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, 20, Eonju-ro 63 gil, Gangnam-gu, Seoul, 06229, South Korea.

Background: Pancreatic cancer has highly aggressive features, such as local recurrence that leads to significantly high morbidity and mortality and recurrence after successful tumour resection. Intraoperative radiation therapy (IORT), which delivers targeted radiation to a tumour bed, is known to reduce local recurrence by directly killing tumour cells and modifying the tumour microenvironment.

Methods: Among 30 patients diagnosed with pancreatic cancer, 17 patients received IORT immediately after surgical resection. We investigated changes in the immune response induced by IORT by analysing the peritoneal fluid (PF) and blood of patients with and without IORT treatment after pancreatic cancer surgery. Further, we treated three pancreatic cell lines with PF to observe proliferation and activity changes.

Results: Levels of cytokines involved in the PI3K/SMAD pathway were increased in the PF of IORT-treated patients. Moreover, IORT-treated PF inhibited the growth, migration, and invasiveness of pancreatic cancer cells. Changes in lymphocyte populations in the blood of IORT-treated patients indicated an increased immune response.

Conclusions: Based on the characterisation and quantification of immune cells in the blood and cytokine levels in the PF, we conclude that IORT induced an anti-tumour effect by activating the immune response, which may prevent pancreatic cancer recurrence.

Clinical Trial Registration: NCT03273374 .
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http://dx.doi.org/10.1186/s12885-021-08807-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8507125PMC
October 2021

Hyperactive and cross-coupled head impulse signs in recurrent strokes: clinical signs of global cerebellar dysfunction.

J Neurol 2021 Oct 5. Epub 2021 Oct 5.

Dizziness Center, Clinical Neuroscience Center, Department of Neurology, Seoul National University Bundang Hospital, Seongnam, South Korea.

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http://dx.doi.org/10.1007/s00415-021-10827-9DOI Listing
October 2021

Diagnostic Value of Straight Head Hanging in Posterior Canal Benign Paroxysmal Positional Vertigo.

J Clin Neurol 2021 Oct;17(4):558-562

Dizziness Center, Seoul National University Bundang Hospital, Seongnam, Korea.

Background And Purpose: To determine the diagnostic value of straight head hanging (SHH) in benign paroxysmal positional vertigo involving the posterior semicircular canal (PC-BPPV).

Methods: We retrospectively included 62 patients (age=56.2±15.0 years, 47 female) with unilateral PC-BPPV who underwent both the Dix-Hallpike maneuver and SHH before receiving canalith repositioning therapy (CRT) between September 2017 and July 2020 at the Dizziness Center of Seoul National University Bundang Hospital in South Korea (16 patients, 25.8%) or the Neurology Outpatient Clinic of Aerospace Central Hospital in China (46 patients, 74.2%). SHH was performed before (=29, group A) or after (=33, group B) the Dix-Hallpike maneuver.

Results: Torsional upbeat nystagmus typical of PC-BPPV was induced during SHH in 52 (83.9%) patients, and the incidence of this type of positional nystagmus did not differ between the groups A and B (79.3% vs. 87.9%, =0.569). The maximum slow-phase velocity of the induced upbeat nystagmus was higher during SHH than during the Dix-Hallpike maneuver toward the lesion side [range=2.0-60.0°/s (median=18.5°/s) vs. range=2.7-40.0°/s (median=13.4°/s), <0.001]. Reversal of the positional nystagmus was observed upon resuming the sitting position after SHH in 47 (75.8%) patients and after the Dix-Hallpike maneuver in 54 (87.7%) patients, with no significant difference between the groups (=0.082).

Conclusions: SHH is effective for diagnosing PC-BPPV. Given its simplicity, SHH may be performed before the Dix-Hallpike maneuver, and CRT may be attempted thereafter when the typical positional nystagmus for unilateral PC-BPPV is induced during SHH.
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http://dx.doi.org/10.3988/jcn.2021.17.4.558DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490902PMC
October 2021

Chasing the structural diversity of the transcription regulator HigA2.

IUCrJ 2021 Sep 24;8(Pt 5):823-832. Epub 2021 Aug 24.

Centre for Biomolecular Sciences, School of Pharmacy, University of Nottingham, Nottingham, United Kingdom.

Transcription factors are the primary regulators of gene expression and recognize specific DNA sequences under diverse physiological conditions. Although they are vital for many important cellular processes, it remains unclear when and how transcription factors and DNA interact. The antitoxin from a toxin-antitoxin system is an example of negative transcriptional autoregulation: during expression of the cognate toxin it is suppressed through binding to a specific DNA sequence. In the present study, the antitoxin HigA2 from M37Rv was structurally examined. The crystal structure of HigA2 comprises three sections: an N-terminal autocleavage region, an α-helix bundle which contains an HTH motif, and a C-terminal β-lid. The N-terminal region is responsible for toxin binding, but was shown to cleave spontaneously in its absence. The HTH motif performs a key role in DNA binding, with the C-terminal β-lid influencing the interaction by mediating the distance between the motifs. However, HigA2 exhibits a unique coordination of the HTH motif and no DNA-binding activity is detected. Three crystal structures of HigA2 show a flexible alignment of the HTH motif, which implies that the motif undergoes structural rearrangement to interact with DNA. This study reveals the molecular mechanisms of how transcription factors interact with partner proteins or DNA.
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http://dx.doi.org/10.1107/S2052252521007715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8420761PMC
September 2021

Stimulation of Toll-Like Receptor 3 Diminishes Intracellular Growth of Typhimurium by Enhancing Autophagy in Murine Macrophages.

Metabolites 2021 Sep 4;11(9). Epub 2021 Sep 4.

Department of Biological Sciences, Kangwon National University, Chuncheon 24341, Korea.

The serovar Typhimurium ( Typhimurium) is a facultative Gram-negative bacterium that causes acute gastroenteritis and food poisoning. . Typhimurium can survive within macrophages that are able to initiate the innate immune response after recognizing bacteria via various pattern-recognition receptors (PRRs), such as Toll-like receptors (TLRs). In this study, we investigated the effects and molecular mechanisms by which agonists of endosomal TLRs-especially TLR3-contribute to controlling . Typhimurium infection in murine macrophages. Treatment with polyinosinic:polycytidylic acid (poly(I:C))-an agonist of TLR3-significantly suppressed intracellular bacterial growth by promoting intracellular ROS production in . Typhimurium-infected cells. Pretreatment with diphenyleneiodonium (DPI)-an NADPH oxidase inhibitor-reduced phosphorylated MEK1/2 levels and restored intracellular bacterial growth in poly(I:C)-treated cells during . Typhimurium infection. Nitric oxide (NO) production increased through the NF-κB-mediated signaling pathway in poly(I:C)-treated cells during . Typhimurium infection. Intracellular microtubule-associated protein 1A/1B-light chain 3 (LC3) levels were increased in poly(I:C)-treated cells; however, they were decreased in cells pretreated with 3-methyladenine (3-MA)-a commonly used inhibitor of autophagy. These results suggest that poly(I:C) induces autophagy and enhances ROS production via MEK1/2-mediated signaling to suppress intracellular bacterial growth in . Typhimurium-infected murine macrophages, and that a TLR3 agonist could be developed as an immune enhancer to protect against . Typhimurium infection.
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http://dx.doi.org/10.3390/metabo11090602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8466172PMC
September 2021

Acute respiratory distress syndrome caused by carbon monoxide poisoning and inhalation injury recovered after extracorporeal membrane oxygenation along with direct hemoperfusion with polymyxin B-immobilized fiber column: a case report.

J Med Case Rep 2021 Sep 15;15(1):456. Epub 2021 Sep 15.

Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan, 135-710, Korea.

Background: Inhalation injury from smoke or chemical products and carbon monoxide poisoning are major causes of death in burn patients from fire accidents. Respiratory tract injuries from inhalation injury and carbon monoxide poisoning can lead to acute respiratory distress syndrome and cytokine storm syndrome. In the case of acute respiratory failure needing mechanical ventilation accompanied by cytokine storm, mortality is high and immediate adequate treatment at the emergency department is very important.

Case Presentation: This report describes a case of acute respiratory distress syndrome and cytokine storm followed by carbon monoxide poisoning in a 34-year-old Korean male patient who was in a house fire, and was successfully treated by extracorporeal membrane oxygenation and direct hemoperfusion with polymyxin B-immobilized fiber column at emergency department.

Conclusions: To prevent mortality in acute respiratory distress syndrome with cytokine storm from inhalation injury and to promote a better prognosis, we suggest that early implication of extracorporeal membranous oxygenation along with direct hemoperfusion with polymyxin B-immobilized fiber column even at the emergency department should be considered.
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http://dx.doi.org/10.1186/s13256-021-03023-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8439957PMC
September 2021

Serum Folliculin Is Related to Lower Pulmonary Function in Patients With Asthma.

Allergy Asthma Immunol Res 2021 Sep;13(5):822-826

Department of Allergy and Clinical Immunology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

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http://dx.doi.org/10.4168/aair.2021.13.5.822DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419642PMC
September 2021

Effects of 1α,25-Dihydroxyvitamin D on the Pharmacokinetics of Procainamide and Its Metabolite N-Acetylprocainamide, Organic Cation Transporter Substrates, in Rats with PBPK Modeling Approach.

Pharmaceutics 2021 Jul 25;13(8). Epub 2021 Jul 25.

College of Pharmacy, Gachon University, Incheon 21936, Korea.

In this study, possible changes in the expression of rat organic cationic transporters (rOCTs) and rat multidrug and toxin extrusion proteins (rMATEs) following treatment with 1α,25-dihydroxyvitamin D (1,25(OH)D) were investigated. Rats received intraperitoneal administrations of 1,25(OH)D for four consecutive days, and the tissues of interest were collected. The mRNA expression of rOCT1 in the kidneys was significantly increased in 1,25(OH)D-treated rats compared with the control rats, while the mRNA expressions of rOCT2 and rMATE1 in the kidneys, rOCT1 and N-acetyltransferase-II (NAT-II) in the liver, and rOCT3 in the heart were significantly decreased. Changes in the protein expression of hepatic rOCT1 and renal rOCT2 and rMATE1 were confirmed by western blot analysis. We further evaluated the pharmacokinetics of procainamide (PA) hydrochloride and its major metabolite N-acetyl procainamide (NAPA) in the presence of 1,25(OH)D. When PA hydrochloride was administered intravenously at a dose 10 mg/kg to 1,25(OH)D-treated rats, a significant decrease in renal and/or non-renal clearance of PA and NAPA was observed. A physiological model for the pharmacokinetics of PA and NAPA in rats was useful for linking changes in the transcriptional and translational expressions of rOCTs and rMATE1 transporters to the altered pharmacokinetics of the drugs.
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http://dx.doi.org/10.3390/pharmaceutics13081133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402143PMC
July 2021

Umbelliferone Ameliorates Benign Prostatic Hyperplasia by Inhibiting Cell Proliferation and G1/S Phase Cell Cycle Progression through Regulation of STAT3/E2F1 Axis.

Int J Mol Sci 2021 Aug 21;22(16). Epub 2021 Aug 21.

Department of Pharmacology, College of Korean Medicine, Sang-ji University, Wonju-si 26339, Korea.

Umbelliferone (UMB), also known as 7-hydroxycoumarin, is a derivative of coumarin, which is widely found in many plants such as carrots, coriander, and garden angelica. Although many studies have already revealed the various pharmacological properties of UMB, its effect on benign prostatic hyperplasia (BPH) remains unclear. Therefore, the present study aimed to elucidate the underlying mechanism of the anti-proliferative effect of UMB in a human benign prostatic hyperplasia cell line (BPH-1), as well as its ameliorative effect on BPH in testosterone propionate (TP)-induced rats. The results showed that UMB exerts an anti-proliferative effect in BPH-1 cells by modulating the signal transducer and activator of transcription 3 (STAT3)/E2F transcription factor 1 (E2F1) axis. UMB treatment not only inhibited androgen/androgen receptor (AR) signaling-related markers, but also downregulated the overexpression of G1/S phase cell cycle-related markers. In TP-induced rats, UMB administration demonstrated an anti-BPH effect by significantly reducing prostate size, weight, and epithelial thickness. In addition, UMB suppressed cell proliferation by reducing the expression of proliferating cell nuclear antigen (PCNA) and p-STAT3 (Tyr 705) in prostate tissue following TP injection. These findings suggest that UMB has pharmacological effects against BPH.
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http://dx.doi.org/10.3390/ijms22169019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8396462PMC
August 2021

Anti-Obesity Drug Orlistat Alleviates Western-Diet-Driven Colitis-Associated Colon Cancer via Inhibition of STAT3 and NF-κB-Mediated Signaling.

Cells 2021 08 11;10(8). Epub 2021 Aug 11.

Department of Pharmacology, College of Korean Medicine, Sangji University, 83 Sangjidae-gil, Wonju-si 26339, Gangwon-do, Korea.

Many researchers have argued that Western diet (WD)-induced obesity accelerates inflammation and that inflammation is a link between obesity and colorectal cancer (CRC). This study investigated the effect of WDs on the development and progression of colitis-associated colon cancer (CAC) and the efficacy of the anti-obesity agent orlistat on WD-driven CAC in mice. The results revealed that the WD exacerbated CAC in azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced mice, which showed increased mortality, tumor formation, and aggravation of tumor progression. Furthermore, WD feeding also upregulated inflammation, hyperplasia, and tumorigenicity levels through the activation of STAT3 and NF-κB signaling in an AOM/DSS-induced mouse model. In contrast, treatment with orlistat increased the survival rate and alleviated the symptoms of CAC, including a recovery in colon length and tumor production decreases in WD-driven AOM/DSS-induced mice. Additionally, orlistat inhibited the extent of inflammation, hyperplasia, and tumor progression via the inhibition of STAT3 and NF-κB activation. Treatment with orlistat also suppressed the β-catenin, slug, XIAP, Cdk4, cyclin D, and Bcl-2 protein levels in WD-driven AOM/DSS-induced mice. The results of this study indicate that orlistat alleviates colon cancer promotion in WD-driven CAC mice by suppressing inflammation, especially by inhibiting STAT3 and NF-κB activation.
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http://dx.doi.org/10.3390/cells10082060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394553PMC
August 2021

Significance of descriptive symptoms and signs and clinical parameters as predictors of neuropathic cancer pain.

PLoS One 2021 17;16(8):e0252781. Epub 2021 Aug 17.

Medical Affairs, Internal Medicine, Pfizer Pharmaceuticals Korea Ltd., Seoul, South Korea.

Purpose: Evaluation of symptoms and signs for the management of neuropathic cancer pain (NCP) is challenging. This study aimed to identify clinical predictors of NCP and symptoms and signs most relevant of those in Korean patients.

Methods: This nationwide, descriptive, cross-sectional, multicenter, observational study included 2,003 cancer patients aged ≥20 years who reported a visual analog scale (VAS) score ≥1 for pain and provided informed consent for participation. The Douleur Neuropathic (DN4) questionnaire (score ≥4) was used to determine symptoms and signs as well as the presence of NCP.

Results: The prevalence of NCP was associated with age <65 years [OR, 1.57; 95% CI, 1.270-1.934], disease duration >6 months (OR, 1.57; 95% CI, 1.232-2.012), stage IV cancer (OR, 0.75; 95% CI, 0.593-0.955), history of chemotherapy (OR, 1.74; 95% CI, 1.225-2.472), and moderate-to-severe cancer pain (OR, 2.05; 95% CI, 1.671-2.524) after multivariate analysis. The most common descriptive symptoms of NCP were tingling, electric shock, and pins and needles. For NCP patients in the presence or absence of the clinical predictors, pins and needles (p = 0.001) and painful cold (p<0.001) symptoms were significantly frequent in patients with moderate-to-severe pain. Tingling, numbness, and touch hypoesthesia (p = 0.022, 0.033, 0.024, respectively) were more frequent in those with longer cancer duration and hyperesthesia (p = 0.024) was more frequent in young patients.

Conclusion: Age <65 years, disease duration >6 months, stage IV cancer, history of chemotherapy, and moderate-to-severe cancer pain, were identified as predictors of NCP. Some symptoms and signs of NCP were associated with these predictors. Further studies are warranted on the pathogenesis and management of NCP with respect to the symptoms and signs, and factors associated with pain severity in Korean patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252781PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8370612PMC
November 2021

Treatment and Outcomes of Metastatic Pancreatic Cancer in Elderly Patients.

Chemotherapy 2021 4;66(4):107-112. Epub 2021 Aug 4.

Department of Internal Medicine, Hallym University Medical Center, Hallym University College of Medicine, Hwaseong-si, Republic of Korea.

Background And Aims: Although pancreatic cancers are common in older age-groups, the prognosis remains poor due to limited studies on treatment approaches and outcomes in a given population. We aimed to examine treatment patterns and their outcomes in older patients with metastatic pancreatic cancer in a real-world context.

Materials And Methods: We conducted a retrospective study including 167 patients with metastatic pancreatic cancer (aged ≥70 years and male/female: 78/89) between January 2010 and July 2015. Patients' retrieved data from medical records were analyzed according to treatment types, followed by a review of clinicopathologic variables and treatment outcomes.

Results: Of the 167 eligible patients for the study, only 21.6% (n = 36) received palliative chemotherapy. The median age of the chemotherapy group was 74.0 years and 78.6 years for the supportive care group. The median survival of the chemotherapy group was 9.2 months (range: 1.0-24.9 months), compared with that of the supportive care group, which was 2.3 months (range: 0.1-31.8 months). Among the patients in the chemotherapy group, 50% (n = 18) received gemcitabine-based double therapy, and 30% patients (n = 9) received second-line chemotherapy.

Conclusions: Our results showed that older patients with metastatic pancreatic cancer were less likely to receive chemotherapy. However, the survival benefit from chemotherapy was comparable to that of younger patients' counterpart. Thus, further study involving identification of older patients who would benefit from cytotoxic chemotherapy is needed.
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http://dx.doi.org/10.1159/000517245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8619775PMC
November 2021

Comprehensive analysis of peripheral T-cell and natural killer/T-cell lymphoma in Asian patients: A multinational, multicenter, prospective registry study in Asia.

Lancet Reg Health West Pac 2021 May 22;10:100126. Epub 2021 Mar 22.

Department of Internal Medicine, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, South Korea.

Background: Peripheral T-cell lymphomas (PTCLs) are uncommon and their frequency is regionally heterogeneous. Several studies have been conducted to evaluate the clinical features and treatment outcomes of this disease entity, but the majority of these were conducted in limited areas, making it difficult to comprehensively analyze their relative frequency and clinical features. Furthermore, no consensus treatment for PTCLs has been established. Therefore, we conducted an Asia-specific study to understand the relative frequency of PTCLs and assess treatments and their outcomes in Asian patients.

Methods: We performed a multinational, multicenter, prospective registry of adult patients with PTCLs that was named as the International Cooperative non-Hodgkin T-cell lymphoma prospective registry study where thirty-two institutes from six Asian countries and territories (Korea, China, Taiwan, Singapore, Malaysia, and Indonesia) participated.

Findings: A total of 486 patients were registered between April 2016 and February 2019, and more than a half of patients (57%) had stage III or IV. Extranodal natural killer (NK)/T- cell lymphoma was the most common subtype ( = 139,28.6%), followed by angioimmunoblastic T-cell lymphoma (AITL,  = 120,24.7%), PTCL-not otherwise specified (PTCL-NOS,  = 101,20.8%), ALK-positive anaplastic large cell lymphoma (ALCL,  = 34,6.9%), and ALK-negative ALCL ( = 30,6.2%). The median progression-free survival (PFS) and overall survival (OS) were 21.1 months (95% CI,10.6-31.6) and 83.6 months (95% CI, 56.7-110.5), respectively. Upfront use of combined treatment with chemotherapy and radiotherapy showed better PFS than chemotherapy alone in localized ENKTL whereas consolidation with upfront autologous stem cell transplantation (SCT) provided longer PFS in advance stage ENKTL. In patients with PTCLs other than ENKTL, anthracycline-containing chemotherapies were widely used, but the outcome of those regimens was not satisfactory, and upfront autologous SCT was not significantly associated with survival benefit, either. The treatment outcome of salvage chemotherapy was disappointing, and none of the salvage strategies showed superiority to one another.

Interpretation: This multinational, multicenter study identified the relative frequency of each subtype of PTCLs across Asian countries, and the survival outcomes according to the therapeutic strategies currently used.

Funding: Samsung Biomedical Research Institute.
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http://dx.doi.org/10.1016/j.lanwpc.2021.100126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315366PMC
May 2021

Ultra-low-dose radiation treatment for early-stage ocular adnexal MALT lymphoma.

Eur J Ophthalmol 2021 Jul 28:11206721211035622. Epub 2021 Jul 28.

Department of Internal Medicine, Hallym University College of Medicine, Hallym University Sacred Heart Hospital, Anyang, Korea.

Purpose: To investigate the long-term outcomes of ultra-low-dose (4 Gy) radiation treatment (RT) in patients with early-stage ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma.

Methods: This retrospective case series includes eight patients with ocular adnexal MALT lymphoma who received ultra-low-dose RT at a single tertiary referral center between March 2016 and February 2018. Response to treatment and the time taken to respond were analyzed.

Results: Of the eight patients (three men, five women), seven patients had conjunctival lymphoma (T1N0M0), and one patient had orbital lymphoma (T2N0M0). Six patients with T1 disease showed complete response (CR), and the median time to CR was 4.5 months (range 2-5). Partial response was achieved in the remaining two patients (one each with T1 and T2). During the median follow-up period of 44 months (range 30-54), none of the patients had a relapse or needed additional treatment. RT was well-tolerated in all patients with no ocular complications, including cataracts and dry eye.

Conclusion: This case series suggests that ultra-low-dose RT is effective and well-tolerated in patients with early-stage ocular adnexal MALT lymphoma. Further studies with a larger sample size and long-term follow-up are needed to evaluate the local control rate and disease-free survival precisely.
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http://dx.doi.org/10.1177/11206721211035622DOI Listing
July 2021

Cutaneous T-cell lymphoma in Asian patients: a multinational, multicenter, prospective registry study in Asia.

Int J Hematol 2021 Sep 24;114(3):355-362. Epub 2021 Jul 24.

Department of Internal Medicine, Division of Hemato-Oncology, Kangdong Sacred Heart Hospital, Hallym University, Seoul, South Korea.

Cutaneous T-cell lymphomas (CTCLs) are a group of T-cell lymphomas with low incidence. Due to their indolent characteristics, treatment strategies have not yet been established for advanced CTCLs. In this study, relative incidence of CTCLs in Asia was estimated and the therapeutic outcomes presented based on various treatments currently used in clinics for advanced CTCLs. As part of a prospective registry study of peripheral T-cell lymphoma (PTCL) conducted across Asia, including Korea, China, Taiwan, Singapore, Malaysia, and Indonesia, subgroup analysis was performed for patients with CTCLs. Among 486 patients with PTCL, 37 with CTCL (7.6%) were identified between April 2016 and February 2019. Primary cutaneous ALK-negative anaplastic large cell lymphoma (ALCL, 35.1%) was the most common subtype. With a median follow-up period of 32.1 months, median progression-free survival (PFS) was 53.5 months (95% CI 0.0-122.5), and overall survival was not reached. 14 patients (48.2%) underwent subsequent treatment after the first relapse, but the response rate was 20% with a PFS of 2.2 months (95% CI 0.3-4.0). Six patients received autologous stem cell transplantation (auto-SCT). However, auto-SCT did not result in better outcomes. Additional studies are needed on standard care treatment of advanced or refractory and relapsed CTCLs.
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http://dx.doi.org/10.1007/s12185-021-03179-7DOI Listing
September 2021

Additional Drug Resistance in Patients with Multidrug-resistant Tuberculosis in Korea: a Multicenter Study from 2010 to 2019.

J Korean Med Sci 2021 Jul 5;36(26):e174. Epub 2021 Jul 5.

Department of Internal Medicine, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Korea.

Background: Drug-resistance surveillance (DRS) data provide key information for building an effective treatment regimen in patients with multidrug-resistant tuberculosis (MDR-TB). This study was conducted to investigate the patterns and trends of additional drug resistance in MDR-TB patients in South Korea.

Methods: Phenotypic drug susceptibility test (DST) results of MDR-TB patients collected from seven hospitals in South Korea from 2010 to 2019 were retrospectively analyzed.

Results: In total, 633 patients with MDR-TB were included in the analysis. Of all patients, 361 (57.0%) were new patients. All patients had additional resistance to a median of three anti-TB drugs. The resistance rates of any fluoroquinolone (FQ), linezolid, and cycloserine were 26.2%, 0.0%, and 6.3%, respectively. The proportions of new patients and resistance rates of most anti-TB drugs did not decrease during the study period. The number of additional resistant drugs was significantly higher in FQ-resistant MDR-TB than in FQ-susceptible MDR-TB (median of 9.0 vs. 2.0). Among 26 patients with results of minimum inhibitory concentrations for bedaquiline (BDQ) and delamanid (DLM), one (3.8%) and three (11.5%) patients were considered resistant to BDQ and DLM with interim critical concentrations, respectively. Based on the DST results, 72.4% and 24.8% of patients were eligible for the World Health Organization's longer and shorter MDR-TB treatment regimen, respectively.

Conclusion: The proportions of new patients and rates of additional drug resistance in patients with MDR-TB were high and remain stable in South Korea. A nationwide analysis of DRS data is required to provide effective treatment for MDR-TB patients in South Korea.
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http://dx.doi.org/10.3346/jkms.2021.36.e174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258238PMC
July 2021

Anti‑angiogenic effect of mountain ginseng and : Comparison with farm‑cultivated ginseng.

Mol Med Rep 2021 Aug 29;24(2). Epub 2021 Jun 29.

Korean Medicine R&D Team 1, National Institute for Korean Medicine Development (NIKOM), Gyeongsan 38540, Republic of Korea.

Mountain ginseng () has been used for cancer patient therapy in Northeast Asia. Although it is well known that cancer cells are able to induce angiogenesis, the effect of mountain ginseng on angiogenesis is still unknown. In the present study, we investigated whether ethanolic extract of mountain ginseng (MGE) could inhibit angiogenesis in and models. In comparison with farm‑cultivated ginseng extract (FGE), MGE more strongly inhibited cell migration and formation of capillary‑like network within non‑cytotoxic ranges in SVEC4‑10 cells. In addition, MGE dose‑dependently suppressed Transwell cell migration of the cells. Moreover, MGE reduced the phosphorylation and expression of VEGF‑R2 as well as the phosphorylation of FAK, Src, Akt and ERK, the intermediate proteins in the VEGF‑R2 signaling cascade, in the cells. As expected, MGE dramatically decreased hemoglobin content in Matrigel plugs in mice. In conclusion, MGE possesses stronger anti‑angiogenic properties than FGE in vascular endothelial cells. Such effect of MGE is correlated with inhibition of activation of the VEGF‑R2 signaling pathway. Therefore, the novel features of MGE may be helpful for understanding its anticancer mechanism for the treatment of cancer patients.
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http://dx.doi.org/10.3892/mmr.2021.12254DOI Listing
August 2021

Preliminary Validation of a Continuum Model for Dimple Patterns on Polyethylene Naphthalate via Ar Ion Beam Sputtering.

Polymers (Basel) 2021 Jun 10;13(12). Epub 2021 Jun 10.

Department of Nano-Bio Convergence, Korea Institute of Materials Science, 797 Changwondae-ro, Changwon 51508, Korea.

This work reports the self-organization of dimple nanostructures on a polyethylene naphthalate (PEN) surface where an Ar ion beam was irradiated at an ion energy of 600 eV. The peak-to-peak roughness and diameter of dimple nanostructures were 29.1~53.4 nm and 63.4~77.6 nm, respectively. The electron energy loss spectrum at the peaks and troughs of dimples showed similar C=C, C=O, and O=CH bonding statuses. In addition, wide-angle X-ray scattering showed that Ar ion beam irradiation did not induce crystallization of the PEN surface. That meant that the self-organization on the PEN surface could be due to the ion-induced surface instability of the amorphous layer and not due to the partial crystallinity differences of the peaks and valleys. A nonlinear continuum model described surface instability due to Ar ion-induced sputtering. The Kuramoto-Sivashinsky model reproduced the dimple morphologies numerically, which was similar to the experimentally observed dimple patterns. This preliminary validation showed the possibility that the continuum equation used for metal and semiconductor surfaces could be applied to polymer surfaces where ion beam sputtering occurred.
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http://dx.doi.org/10.3390/polym13121932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230451PMC
June 2021

Therapeutic effects of Gambi-jung for the treatment of obesity.

Biomed Pharmacother 2021 Sep 25;141:111838. Epub 2021 Jun 25.

Department of Pharmacology, College of Korean Medicine, Sangji University, Wonju, Gangwon-do 26339, Republic of Korea. Electronic address:

Obesity is known as metabolic syndrome and it affects many tissues including adipose tissue, liver, and central nervous system (CVS). Gambi-jung (GBJ) is a modified prescription of Taeumjowi-tang (TJT), which has been used to treat obesity in Korea. GBJ is composed of 90% Ephedra sinica Stapf (ES). Therefore, the present study was designed to assess the antiobesity effects of GBJ and to compare the effects of GBJ and ES on obesity. GBJ administration remarkably reduced the body weight, Body mass index (BMI), and body fat percentage compared to the ES administration in human subjects. GBJ-treated mice had lower white adipose tissue (WAT) amounts than ES-treated mice. GBJ and ES administration enhanced adenosine monophosphate-activated protein kinase (AMPK) expression in 3T3-L1 adipocytes, epididymal WAT and liver of HFD-induced obese mice. Moreover, GBJ and ES reduced food intake by suppressing the mRNA levels of orexigenic peptides, agouti-related protein (AgRP) and neuropeptide-Y (NPY), as well as AMPK in the brain of HFD-induced obese mice. Furthermore, GBJ-treated mice had dramatically lower expression of macrophage marker F4/80 in epididymal WAT than those of ES-treated mice. Based on these results, we suggest the use of GBJ as a natural drug to control weight gain.
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http://dx.doi.org/10.1016/j.biopha.2021.111838DOI Listing
September 2021

Influence of metallization process on solution-processed InGaZnO thin film transistors.

Nanotechnology 2021 Jul 13;32(40). Epub 2021 Jul 13.

Department of Physics, Pusan National University, Busan 46241, Republic of Korea.

Low-temperature solution-processed InGaZnO (IGZO) thin film transistors (TFTs) have recently attracted significant attention as the next-generation flexible display TFTs, owing to their high transparency, high electrical performance, low-cost fabrication, and large-area scalability. However, solution-processed amorphous IGZO TFTs have several drawbacks, such as poor film quality or low stability, and have been studied with view to improving the device performance. One of the critical components determining device characteristics is the metallization process, which we systematically studied using aluminum (Al) source and drain electrodes. The electrical properties were measured for different channel lengths and evaluated using the threshold voltage () and subthreshold swing (SS). Al electrodes directly affect the channel region, enhancing the electron density because of the doping effect from Al and oxygen vacancy-related oxidation of Al and causing an abnormal negative shift of, which is confirmed by the component analysis via various spectroscopies. To understand and improve the TFT characteristics, we conducted a low-temperature post-annealing process and polymer passivation and succeeded in movingfrom over 150 V to near 0 V and remarkably improved SS. This study discovered that the influence of source-drain metallization on the channel region determines the device characteristics through the close relation between metal oxidation and the number of oxygen vacancies.
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http://dx.doi.org/10.1088/1361-6528/ac0eafDOI Listing
July 2021

Immunoglobulin gene rearrangement in Koreans with multiple myeloma: Clonality assessment and repertoire analysis using next-generation sequencing.

PLoS One 2021 24;16(6):e0253541. Epub 2021 Jun 24.

Department of Laboratory Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, South Korea.

Introduction: We assessed the applicability of next-generation sequencing (NGS)-based IGH/IGK clonality testing and analyzed the repertoire of immunoglobulin heavy chain (IGH) or immunoglobulin kappa light chain (IGK) gene usage in Korean patients with multiple myeloma (MM) for the first time.

Methods: Fifty-nine bone marrow samples from 57 Korean patients with MM were analyzed, and NGS-based clonality testing that targeted the IGH and IGK genes was performed using IGH FR1 and IGK primer sets.

Results: Clonal IGH and IGK rearrangements were observed in 74.2% and 67.7% of samples from Korean patients with kappa-restricted MM, respectively (90.3% had one or both), and in 60.7% and 95.5% of samples from those with lambda-restricted MM, respectively (85.7% had one or both). In total, 88.1% of samples from Koreans with MM had clonal IGH and/or IGK rearrangement. Clonal rearrangement was not significantly associated with the bone marrow plasma cells as a proportion of all BM lymphoid cells. IGHV3-9 (11.63%) and IGHV4-31 (9.30%) were the most frequently reported IGHV genes and were more common in Koreans with MM than in Western counterparts. IGHD3-10 and IGHD3-3 (13.95% each) were the most frequent IGHD genes; IGHD3-3 was more common in Koreans with MM. No IGK rearrangement was particularly prevalent, but single IGKV-J rearrangements were less common in Koreans with kappa-restricted MM than in Western counterparts. IGKV4-1 was less frequent in Koreans regardless of light chain type. Otherwise, the usages of the IGH V, D, and J genes and of the IGK gene were like those observed in previous Western studies.

Conclusion: NGS-based IGH/IGK clonality testing ought to be applicable to most Koreans with MM. The overrepresentation of IGHV3-9, IGHV4-31, and IGHD3-3 along with the underrepresentation of IGKV4-1 and the differences in IGK gene rearrangement types suggest the existence of ethnicity-specific variations in this disease.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253541PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224885PMC
November 2021

Isoniazid Population Pharmacokinetics and Dose Recommendation for Korean Patients With Tuberculosis Based on Target Attainment Analysis.

J Clin Pharmacol 2021 Dec 26;61(12):1567-1578. Epub 2021 Jul 26.

Center for Personalized Precision Medicine of Tuberculosis (cPMTb), Inje University College of Medicine, Busan, Republic of Korea.

The wide variability of isoniazid (INH) pharmacokinetics is mainly attributed to the trimodal N-acetyltransferase 2 (NAT2) acetylator phenotype, that is, rapid, intermediate, and slow. Consequently, a uniform INH dose in current clinical practice may lead to treatment failure and emergence of drug resistance. There is a lack of studies on specific doses of INH for different NAT2 acetylator phenotypes among tuberculosis (TB) patients. Therefore, we aimed to provide insight into the optimal dosing of INH for each NAT2 acetylator phenotype with respect to the probability of achieving a pharmacokinetic (PK)/pharmacodynamic target. PK, the NAT2 genotype, and clinical data were collected in a multicenter prospective cohort study conducted at 13 clinical centers in Korea. Population PK modeling and simulation were carried out. Data from 454 TB patients were divided into a training data set and a test data set at a ratio of 4 to 1. The PK of the training data were best described by a 2-compartment model with allometric scaling for body size effect. Importantly, NAT2 acetylator phenotypes significantly affected the apparent clearance. Our model, which provided better predictive performance compared with previously published models, was evaluated by external validation using the test set. The simulation for assessing target efficacy and toxicity indicated that the best INH dosing regimens for Korean tuberculosis patients were once-daily doses of 400, 300, and 200 mg for rapid, intermediate, and slow acetylators, respectively. In conclusion, our study provides a step forward in precision dosing for antituberculosis management.
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http://dx.doi.org/10.1002/jcph.1931DOI Listing
December 2021

Can Dyssynergia of Vestibulosympathetic and Baroreflexes Cause Vestibular Syncope? The Hypothesis Based on the Velocity-Storage Function.

Cerebellum 2021 Jun 22. Epub 2021 Jun 22.

Dizziness Center, Clinical Neuroscience Center, Department of Neurology, Seoul National University Bundang Hospital, Seongnam, South Korea.

The mechanism of vestibular syncope, the syncope occurring during the vertigo attacks, remains uncertain. This study aims to clarify the mechanism of vestibular syncope by pursuing the function of vestibular system in cardiovascular autonomic control and by defining neuro-hemodynamic changes in vestibular syncope. By integrating the velocity-storage (VS) circuit in the brainstem and cerebellum, we propose that the vestibular syncope develops as a result of dyssynergia of the vestibulosympathetic and baroreflexes in which centrally estimated downward inertial acceleration during the vertigo attacks acts as a trigger. Recognition of the vestibular disorders as a possible cause of syncope would allow proper managements for prevention of further syncope and related complications in patients with vestibular disorders.
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http://dx.doi.org/10.1007/s12311-021-01296-xDOI Listing
June 2021

Forecast the Exacerbation in Patients of Chronic Obstructive Pulmonary Disease with Clinical Indicators Using Machine Learning Techniques.

Diagnostics (Basel) 2021 May 4;11(5). Epub 2021 May 4.

College of AI Convergence/Institute of Digital Anti-Aging Healthcare/u-HARC, Inje University, Gimhae 50834, Korea.

Preventing exacerbation and seeking to determine the severity of the disease during the hospitalization of chronic obstructive pulmonary disease (COPD) patients is a crucial global initiative for chronic obstructive lung disease (GOLD); this option is available only for stable-phase patients. Recently, the assessment and prediction techniques that are used have been determined to be inadequate for acute exacerbation of chronic obstructive pulmonary disease patients. To magnify the monitoring and treatment of acute exacerbation COPD patients, we need to rely on the AI system, because traditional methods take a long time for the prognosis of the disease. Machine-learning techniques have shown the capacity to be effectively used in crucial healthcare applications. In this paper, we propose a voting ensemble classifier with 24 features to identify the severity of chronic obstructive pulmonary disease patients. In our study, we applied five machine-learning classifiers, namely random forests (RF), support vector machine (SVM), gradient boosting machine (GBM), XGboost (XGB), and K-nearest neighbor (KNN). These classifiers were trained with a set of 24 features. After that, we combined their results with a soft voting ensemble (SVE) method. Consequently, we found performance measures with an accuracy of 91.0849%, a precision of 90.7725%, a recall of 91.3607%, an F-measure of 91.0656%, and an AUC score of 96.8656%, respectively. Our result shows that the SVE classifier with the proposed twenty-four features outperformed regular machine-learning-based methods for chronic obstructive pulmonary disease (COPD) patients. The SVE classifier helps respiratory physicians to estimate the severity of COPD patients in the early stage, consequently guiding the cure strategy and helps the prognosis of COPD patients.
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http://dx.doi.org/10.3390/diagnostics11050829DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147791PMC
May 2021

Negative Prognostic Implication of Promoter Mutations in Human Papillomavirus-Negative Tonsillar Squamous Cell Carcinoma Under the New 8th AJCC Staging System.

Indian J Surg Oncol 2021 Apr 5;12(Suppl 1):134-143. Epub 2020 Sep 5.

Department of Hematological Oncology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Republic of Korea.

Telomerase reverse transcriptase gene promoter () mutation is a potential candidate for pathogenesis and therapeutic target of tonsillar squamous cell carcinomas (TSCCs) in association with human papillomavirus (HPV). Their clinical relevance has not been validated under the new 8th American Joint Committee on Cancer (AJCC) staging system. We analyzed real-time peptide nucleic acid-mediated PCR and sequencing methods ( mutation) and real-time PCR-based assay (HPV) in 80 surgically resected TSCCs. The 8th edition staging system improved the stratification of the early and advanced stages and between T or N categories for overall survival over the 7th edition. mutation was found in 7.5%, and HPV in 80.0% of the patients. The majority (83.3%) of mutation cases were HPV-positive TSCCs. Applying the 8th edition staging system, mutation was an independent factor of poor prognosis for disease-free survival (DFS) in TSCC patients, supporting the clinical significance of mutation in tonsil cancer. mutations were also negatively correlated with overall survival and DFS in HPV-negative TSCCs. Conclusively, mutation provides negative prognostic impact on survival of surgically managed tonsil cancers staged with the AJCC 8th edition.
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http://dx.doi.org/10.1007/s13193-020-01200-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8119516PMC
April 2021
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